The major project in this laboratory is to determine the pathogenetic mechanisms of plasmacytoma development in BALB/c mice. The development of this process is dependent upon the genotype of the BALB/c mouse and the participation of specific susceptibility genes. Most conventional strains carry dominant resistance (R) genes. DBA/2, for example, has 3 R genes. We have evidence that one of these is carried on a BALB/c congenic strain carrying the To1-1Alpha locus of DBA/2. Susceptibility to plasmacytoma genes may be mediated by genes controlling the inflammatory responses to pristane (mineral oil). We have shown that the nonsteroidal anti-inflammatory agent indiomethacin, a powerful cyclooxygenase inhibitor, strikingly inhibits pristane and induces plasmacytoma development. These mice, however, do develop oil granulomas and inflammatory exudates. We are attempting to find the biochemical differences between the pristane and pristane-indomethacin oil granulomas. One of the important contributions of the oil granuloma is the provision of growth factors that are required by developing plasmacytoma cells. We have developed a growth dependent transplantable plasma-cytoma line in vitro that reflects a growth factor of macrophage origin. This factor does not appear to be any of the known factors. Accordingly, we are proceeding to isolate and characterize this factor.